a SUPA, School of Physics and Astronomy , University of Edinburgh , Peter Guthrie Tait Road, Edinburgh , EH9 3FD , UK.
b Dipartimento di Fisica , Universita' di Napoli Federico II, INFN Napoli, CNR, SPIN, Complesso Universitario di Monte Sant'Angelo , Naples , Italy.
Nucleus. 2018 Jan 1;9(1):95-103. doi: 10.1080/19491034.2017.1421825.
Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo "Non-equilibrium chromosome looping via molecular slip-links", Physical Review Letters 119 138101 (2017).
染色质环挤压是形成 CTCF 环和拓扑结构域的流行模型。最近的 HiC 数据显示出一种强烈的倾向,有利于稳定环的 CTCF 结合基序的特定排列,而挤压是迄今为止唯一可以解释这种现象的模型。然而,该模型需要一个马达来产生环,尽管黏连蛋白是挤压因子的有力候选物,但尚未找到合适的马达蛋白(或黏连蛋白本身的马达活性)。在这里,我们提出了一个新的假设:没有马达,核内的热运动驱动挤压。我们使用理论建模和计算机模拟来探讨这种扩散挤压是否能够产生环。我们的模拟揭示了一种有趣的棘轮效应(渗透压促进环的生长),并通过与最近的体外和体内测量结果进行比较,表明扩散挤压原则上可以产生与数据中观察到的大小相当的环。
C. A. Brackley、J. Johnson、D. Michieletto、A. N. Morozov、M. Nicodemi、P. R. Cook 和 D. Marenduzzo,“通过分子滑链实现非平衡染色体环化”,物理评论快报 119,138101(2017 年)。